Centre for Cancer Research - Research Publications

Permanent URI for this collection

http://hdl.handle.net/11343/194839

Filters

2002 - 2008 2
2
Reset filters

Settings
Statistics
Citations
Author: Roberts, Andrew × Start date: 2002 × End date: 2009 ×

Search Results

Now showing 1 - 2 of 2
  • Item
    Thumbnail Image
    Renal safety of zoledronic acid with thalidomide in patients with myeloma: a pharmacokinetic and safety sub-study.
    Spencer, A ; Roberts, A ; Kennedy, N ; Ravera, C ; Cremers, S ; Bilic, S ; Neeman, T ; Copeman, M ; Schran, H ; Lynch, K (Springer Science and Business Media LLC, 2008-03-31)
    BACKGROUND: Cases of impaired renal function have been reported in patients who had been treated with both zoledronic acid and thalidomide for myeloma. Hence, we conducted a safety study of zoledronic acid and thalidomide in myeloma patients participating in a trial of maintenance therapy. METHODS: Twenty-four patients who were enrolled in a large randomized trial of thalidomide vs no thalidomide maintenance therapy for myeloma, in which all patients also received zoledronic acid, were recruited to a pharmacokinetic and renal safety sub-study, and followed for up to 16 months. RESULTS: No significant differences by Wilcoxon rank-sum statistic were found in zoledronic acid pharmacokinetics or renal safety for up to 16 months in patients randomized to thalidomide or not. CONCLUSION: In myeloma patients receiving maintenance therapy, the combination of zoledronic acid and thalidomide appears to confer no additional renal safety risks over zoledronic acid alone.
  • Item
    Thumbnail Image
    Dok-related protein negatively regulates T cell development via its RasGTPase-activating protein and Nck docking sites
    Gugasyan, R ; Quilici, C ; I, STT ; Grail, D ; Verhagen, AM ; Roberts, A ; Kitamura, T ; Dunn, AR ; Lock, P (ROCKEFELLER UNIV PRESS, 2002-07-08)
    Downstream of kinase (Dok)-related protein (DokR, also known as p56(dok)/FRIP/Dok-R) is implicated in cytokine and immunoreceptor signaling in myeloid and T cells. Tyrosine phosphorylation induces DokR to bind the signal relay molecules, RasGTPase-activating protein (RasGAP) and Nck. Here, we have examined the function of DokR during hematopoietic development and the requirement for RasGAP and Nck binding sites in its biological function. Retroviral-mediated expression of DokR in bone marrow cells dramatically inhibited their capacity to form colonies in vitro in response to the cytokines macrophage colony-stimulating factor and stem cell factor, whereas responses to interleukin-3 and granulocyte macrophage colony-stimulating factor were only weakly affected. When introduced into lethally irradiated mice, hematopoietic cells expressing DokR showed a drastically reduced capacity to repopulate lymphoid tissues. Most notably, DokR dramatically reduced repopulation of the thymus, in part by reducing the number of T cell precursors seeding in the thymus, but equally, through inhibiting the transition of CD4(-)CD8(-) to CD4(+)CD8(+) T cells. Consequently, the number of mature peripheral T cells was markedly reduced. In contrast, a minimal effect on B cell and myeloid lineage development was observed. Importantly, functional RasGAP and Nck binding sites were found to be essential for the biological effects of DokR in vitro and in vivo.